The present invention relates to the field of analytical chemistry and in particular to a method and calibration sample for calibrating analytical instruments with a standard solution.
Analytical instruments, such as ion mobility spectrometers, gas chromatographs, mass spectrometers, and the like, are used to measure chemical properties or chemical composition of an analyte sample or of an analyte component in a sample. Calibration of analytical instruments is necessary to ensure the continued accuracy of measurements performed by such devices. The present invention provides a novel and useful means of calibrating a large class of analytical instruments, including ion mobility spectrometers, gas chromatographs, mass spectrometers, and the like, which operate internally in the vapor phase, but are capable of analyzing volatile solids and liquids because they are provided with inlet means in which solid or liquid samples can be heated and the volatile analytes therein converted to vapour which is then drawn into the instrument for analysis. Many of the foregoing class of instruments are used outside the laboratory, and in such cases, it is customary to collect samples using a specialized inert device, such as a wipe, filter or the like, and then to insert the entire collection device, containing the sample, into the instrument for analysis. These sample collection methods are employed because they allow non-technical personnel to easily and rapidly collect and analyze representative, uncontaminated, samples. In one embodiment, the present invention provides calibration standards which closely mimic these sampling devices in appearance and mode of use, with similar advantages to the operator.
The calibration procedures commonly used in the prior art require the use of one or more standard solutions to calibrate the measurement of unknown analyte concentrations. These standard solutions, which are carefully made up, under controlled laboratory conditions, so as to contain precisely known concentrations of an analyte.
Several methods of calibrating instruments using standard solutions are well known. The working curve calibration method, for example, effectively creates a plot of the analytical signal from the instrument as a function of analyte concentration, i.e. the response of the instrument. This plot is obtained by measuring the signal from a series of standards of known concentrations. The working curves may then be used to determine the concentration of an unknown analyte sample. Similarly, the standard addition calibration procedure is performed by dividing an unknown sample into two portions, and adding a known amount of the analyte under measurement to one of the portions (also known as xe2x80x9cspikingxe2x80x9d that portion). Both portions of the unknown sample are then analyzed and the difference in responses is due to the additional amount of analyte added to the one portion. This difference thereby provides a calibration point to determine the analyte concentration in the original sample.
Some analytical instruments, particularly those intended for field use by non-technical personnel, do not provide a numeric measure of the amount of analyte in the sample, but only an xe2x80x9cAbsent/Presentxe2x80x9d indication. That is, they determine only that the amount of analyte in a sample is greater or less than a threshold value. Such instruments may erroneously indicate xe2x80x9cAbsentxe2x80x9d when the amount of analyte is above the threshold (False Negative) or xe2x80x9cPresentxe2x80x9d when the amount is below threshold (False Positive). False Negatives occur when the sensitivity of the instrument decreases. False Positives can be caused by electrical or similar disturbances in the instrument, and also by other components in the sample being mis-classified as analyte. Acceptable performance for instruments of this type is usually defined by specifying two quantities, namely, the smallest amount of analyte (often called the xe2x80x9cMinimum Detectable Amountxe2x80x9d) which should give no False Negatives, and the maximum tolerable fraction of False Positive responses to samples which contain no analyte. A set of calibration standards for such instruments consist of two types of sample, one known to contain the Minimum Detectable Amount of analyte, and a xe2x80x9cblankxe2x80x9d, containing no analyte. Advantageously, the blank contains typical amounts of the other materials normally accompanying the analyte, and of any materials which are known to be potential sources of False Positives.
In prior art calibration procedures, the standard solutions of known analyte concentrations (or calibration solutions) are produced, maintained, and eventually supplied to the instruments in liquid form. During calibration, the premixed standard liquid solutions are either injected directly into an instrument using syringes or are spotted on to substrates and thermally desorbed into instruments.
Analytical instruments must often be taken into the field to perform in situ measurements. For example, this may be required for soil or water environmental analyses at contaminated sites, for environmental control in oil refineries, for petrochemical processes, for checking contamination at land fill sites, or for checking for drugs and explosives at customs or border stations. In these situations, a more practical and robust calibration means suitable for operation in these environments is highly desirable. Furthermore, field based analytical instrumentation is being increasingly used by environmental specialists, site cleanup and remedial teams, security or customs agents engaged in drug and explosive interdiction, and other similar individuals. In addition to the absence of controlled laboratory environment, this means that sensitive analytical instruments must be operated and calibrated by individuals who are not trained as analytical technicians or chemists (e.g. customs officers, law enforcement, or security agents screening for drugs and explosives). As a result, a simple and easy calibration technique is also required.
In all these circumstances, conditions are not suitable for the storage, transportation, handling, and accurate dispensing of solutions in liquid form. Consequently, there is a genuine need for a simple, practical, and quick calibration technique which provides a high level of measurement accuracy, especially for instruments which are operated under field conditions away from laboratories and by individuals who are, chemically or analytically speaking, unskilled.
It is an object of the present invention to provide an improved method and apparatus for calibration of analytical instruments, particularly instruments which operate under field conditions away from laboratories or other controlled environments and which may be used by persons without significant skills for carrying out such calibrations by the methods of the prior art.
In a first aspect, the present invention provides a method of providing a calibration sample comprising the steps of:
(a) providing a standard solution containing at least an analyte in a known concentration and a chromatographic phase material; and
(b) impregnating a substrate with the standard solution so that the substrate contains the analyte in a solid phase.
Step (a) can include providing a standard solution containing an explosive analyte material. The explosive analyte material can be selected from the group consisting of: 2,4,6-trinitrotoluene, cyclotrimethylenetrinitramine, pentaerythritol tetranitrate, nitroglycerine, ammonium nitrate, cyclo-tetramethylene-tetranitramine, and tetryl.
Alternatively, step (a) can include providing a standard solution containing an analyte which is a drug or a chromatographic phase material which is a polymer. Such a polymer can be selected from the group consisting of: polydimethylsilane, polymethylsilane, polymethylphenylsilane, polyphenylsilane, and Tenac(copyright).
Preferably, step (a) includes providing a standard solution containing at least one of a dopant, a reactant, and a cleansing agent for an ion mobility spectrometer.
The substrate is preferably formed from a material selected from the group consisting of: fiber glass or polytetrafluoroethylene. More preferably, the substrate material is fiber glass and the method further includes the step of baking the substrate prior to the step of impregnating the substrate.
Conveniently, step (b) comprises adsorbing the standard solution into the substrate.
Preferably, the method further comprises the steps of:
(c) forming the impregnated substrate into sheet material;
(d) cutting the sheet material into calibrant pieces; and
(e) positioning the calibrant pieces on a neutral filter.
The method advantageously further comprises the step of housing the substrate in a card holder to facilitate storage and transportation of the impregnated substrate. Preferably, the step of housing the substrate in a card holder includes the steps of inserting the impregnated substrate into a recessed well located on said card holder and press-fitting an assembly over said substrate to retain the substrate in a fixed position.
Another aspect of the present invention provides a method of calibrating an analytical instrument, the method comprising the steps of providing a calibration sample as defined above and further comprising the steps of
(c) inserting the substrate into a desorption region of the analytical instrument; and
(d) heating the substrate to desorb the analyte.
Advantageously, the substrate is porous and the method further includes the step of sweeping a purge of gas through the substrate during the heating of the substrate in step (d).
Yet another aspect of the present invention provides a method of calibrating an analytical instrument comprising the steps of providing a calibration sample as defined above and further comprising the steps of
(c) forming the impregnated substrate into sheet material;
(d) cutting the sheet material into calibrant pieces;
(e) positioning the calibrant pieces on a neutral filter;
(f) inserting the neutral filter into a desorption region of the analytical instrument; and
(g) heating the substrate to desorb the analyte.
Preferably, the method further comprises the step of providing calibrant pieces suitable for generating a low level analytical instrument output to which the device has been conditioned to classify as a false detection.